Project Summary
The goal of this project is to investigate the cerebrovascular link between traumatic brain injury (TBI) and Alzheimer’s disease, and mechanistically understand the vascular contribution to elevated risks for Alzheimer’s disease in preclinical models of TBI.
Our central hypothesis is that vascular dysfunctions after TBI tip the balance between the production and clearance of Alzheimer’s β-amyloid in brain, and directly contribute to Alzheimer’s pathogenesis and cognitive impairment. We propose to use rodent models of TBI, and determine: i) the cellular and molecular mechanisms by which TBI induces vascular dysfunctions and blood-brain barrier breakdown, and ii) how such vascular dysfunctions impair the clearance of β-amyloid through the cerebrovascular system, and accelerate amyloid pathologies and neurodegeneration.
By understanding the vascular impairment as a direct consequence of TBI, and its negative impact on the amyloid metabolism in the brain, as well as long-term cognitive changes in animals, we hope to build a research resource to bridge the knowledge gap between TBI and Alzheimer’s disease. The outcomes of the proposed studies will provide new insights into the true trigger of Alzheimer’s cascade by TBI, and identify a novel target based on blood-brain barrier and vascular dysfunctions for prognosis detection and potentially intervention of Alzheimer’s pathogenesis in TBI survivors in the future.
